E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Parkinson's disease dyskinesia |
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E.1.1.1 | Medical condition in easily understood language |
Parkinson's disease dyskinesia refers to a group of involuntary movement disorders. Dyskinesia can be anything from a slight tremor of the hands to an uncontrollable movement of the body. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061536 |
E.1.2 | Term | Parkinson's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of IRL790 in Parkinson's disease dyskinesia |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effects of IRL790 on core symptoms of Parkinson's disease.
To evaluate the pharmacokinetics, safety and tolerability of IRL790 in patients with Parkinson's disease dyskinesia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female ≥18 and ≤79 years of age.
2. Signed a current Ethics Committee approved informed consent form.
3. Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria.
4. Waking day dyskinesia of ≥25% determined as a score of ≥2 as per Question 4.1 of the MDS-UPDRS.
5. On a stable regimen of antiparkinson medications for at least 30 days prior to screening, including a levodopa preparation administered not less than three times daily and willing to continue the same doses and regimens during study participation. Rescue medication such as Madopar dispersable and Apomorphine injections are allowed.
6. Taking a maximum of eight regular levodopa intakes per day, excluding bedtime and night time levodopa.
7. Any other current and allowed prescription/non-prescription medications and/or nutritional supplements taken regularly must have been at a stable dose and regimen for at least 30 days prior to screening and the patient must be willing to continue the same doses and regimens during study participation (this criterion does not apply to medications that are being taken pre-study only on an as-needed basis).
8. Patients must be willing and able to avoid direct exposure to sunlight from day 1 to day 28.
9. Able to complete at least one valid 24-hour patient diary at Visit 1. |
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E.4 | Principal exclusion criteria |
1. History of neurosurgical intervention related to Parkinson's disease (e.g. deep brain stimulation).
2. Treatment with pump delivered antiparkinsonian therapy (i.e. subcutaneous apomorphine or levodopa/carbidopa intestinal infusion).
3. History of seizures within two years prior to screening.
4. History of stroke or transient ischemic attack (TIA) within two years prior to screening.
5. History of cancer within five years prior to screening, with the following exceptions: adequately treated non-melanomatous skin cancers, localised bladder cancer, non-metastatic prostate cancer or in situ cervical cancer.
6. Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination (MMSE) score of less than 24 during screening.
7. A Hoehn and Yahr stage of five.
8. Any history of a significant heart condition, or cardiac arrhythmias within the past 5 years, any repolarisation deficits or any other clinically significant abnormal ECG as judged by the Investigator.
9. Severe or ongoing unstable medical condition including a history of poorly controlled diabetes; obesity associated with metabolic syndrome; uncontrolled hypertension; cerebrovascular disease, or any form of clinically significant cardiac disease; clinically significant symptomatic orthostatic hypotension; clinically significant hepatic disease;, renal failure, or a abnormal renal function.
10. Any history of a neurological or other than Parkinson’s disease or a psychiatric disorder, including history of DSM IV diagnosed major depression, or psychosis. Patients with illusions or hallucinations with no loss of insight will be eligible Patients with mild depression who are well controlled on a stable dose of an antidepressant medication for at least 4 weeks before screening will be eligible.
11. Enrolment in any other clinical study involving medication, medical devices or surgical procedures, current or within three months prior to screening visit, or previous participation in the present study. Patients enrolled in non-interventional clinical trials will be eligible. 12. Drug and/or alcohol abuse
13. History of severe drug allergy or hypersensitivity
14. If female, is pregnant or lactating, or has a positive pregnancy test result pre-dose
15. Patients unwilling to use two forms of contraception (one of which being a barrier method see Section 7.3) 90 days for men and 30 days for women after last IMP dose
16. Any planned major surgery within the duration of the study
17. Any other condition or symptoms preventing the patient from entering the study, according to the Investigator’s judgement
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the Unified Dyskinesia Rating Scale (UDysRS) total score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
UDysRS measured at Baseline (Day 1) and week 4 |
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E.5.2 | Secondary end point(s) |
Secondary Endpoints Change in Total Objective Score (III, IV) of the UDysRS
Change in daily "OFF" time as assessed with patient diaries from run-in to Visit 4.
Change in Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score of part III (motor), and sum score of Questions 4.1 and 4.2 in part IV
Exploratory Endpoints Unified Parkinson's Disease Rating Scale (MDS-UPDRS), part I (total score), part II (total score) and part IV (total score)
Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Question 1.2 (Hallucinations and Psychosis)
Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Question 1.6 (Features of dopamine dysregulation syndrome)
Clinician's Global Impression of Change in overall PD symptoms
Daily "ON" time with troublesome dyskinesia as assessed with patient diaries from run-in to Visit 4.
Change in “ON” time as assessed by patient completed 24-hour diaries, from run-in to Visit 4 (Day 28).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Endpoints Change in Total Objective Score (III, IV) of UDysRS from Day 1 to Visit 4
Change in daily "OFF" time as assessed with patient diaries from run-in to Visit 4
Change in MDS-UPDRS total score of part III and sum of score of Questions 4.1 and 4.2 in part IV from Day 1 to Week 4
Exploratory Endpoints MDS-UPDRS Part I, part II and Part IV total scores from Day 1 to Visit 4
MDS-UPDRS Question 1.2 from Day 1 to Visit 4
MDS-UPDRS Question 1.6 from Day 1 to Visit 4
Clinician's Global Impression of Change in overall PD symptoms from Day 1 to Visit 4.
Daily "ON" time assessed by patient diaries from run-in to Visit 4.
Change in “ON” time as assessed by patient completed 24-hour diaries, from run-in to Visit 4.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |